3-3128725-G-C

Variant names:

• chr3-3128725-G-C
• rs334774
• NM_182916.3:c.-27-289G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182916.3(TRNT1):​c.-27-289G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,896 control chromosomes in the GnomAD database, including 21,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (21908 hom., cov: 31)
• Consequence: TRNT1 NM_182916.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.539
• Publications: 2 publications found

Genes affected

TRNT1 (HGNC:17341): (tRNA nucleotidyl transferase 1) The protein encoded by this gene is a CCA-adding enzyme which belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family. This essential enzyme functions by catalyzing the addition of the conserved nucleotide triplet CCA to the 3' terminus of tRNA molecules. Mutations in this gene result in sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

TRNT1 Gene-Disease associations (from GenCC):

• congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• retinitis pigmentosa and erythrocytic microcytosis

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 3-3128725-G-C is Benign according to our data. Variant chr3-3128725-G-C is described in ClinVar as [Benign]. Clinvar id is 669583.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRNT1	NM_182916.3	c.-27-289G>C		intron_variant	Intron 1 of 7	ENST00000251607.11	NP_886552.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRNT1	ENST00000251607.11	c.-27-289G>C		intron_variant	Intron 1 of 7	1	NM_182916.3	ENSP00000251607.6

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77344 AN: 151780 Hom.: 21919 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.571

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.509 AC: 77331 AN: 151896 Hom.: 21908 Cov.: 31 AF XY: 0.501 AC XY: 37154 AN XY: 74218

African (AFR) AF: 0.291 AC: 12032 AN: 41402

American (AMR) AF: 0.465 AC: 7098 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2446 AN: 3468

East Asian (EAS) AF: 0.196 AC: 1014 AN: 5162

South Asian (SAS) AF: 0.434 AC: 2091 AN: 4814

European-Finnish (FIN) AF: 0.568 AC: 5984 AN: 10528

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44594 AN: 67948

Other (OTH) AF: 0.572 AC: 1206 AN: 2110

Alfa AF: 0.452 Hom.: 1435

Bravo AF: 0.490

Asia WGS AF: 0.337 AC: 1176 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.30
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs334774; hg19: chr3-3170409;